Practolol inhibits human skin fibroblast cell mat hydroxyproline accumulation

Abstract

Despite being poorly absorbed practolol (N-4-2-hydroxy-3-(1-methyl-ethyl)-amino propoxy phenyl acetamine) inhibited the accumulation of cell mat hydroxyproline, a measure of collagen synthesis, by human skin fibroblasts (DT2PH) in vitro, (ID50 0.8 X 10(-3) M). The degree of inhibition was dependent on the concentration of practolol used and the incubation time. Neither preinitiation of collagen synthesis nor omitting ascorbic acid from the incubation medium modified this inhibitory action. In contrast, in vitro generated metabolites of practol, using normal and aroclor induced hamster liver preparation, and structural analogues of practolol had no effect on cell mat hydroxyproline levels. Related compounds, propranolol, (1-(isopropylamino)-3(1-naphthyl-oxy)2-propranolol), and paracetamol, (N-(4-hydroxyphenyl)acetamide), both inhibited hydroxyproline levels. Fibroblasts derived from uninvolved skin of a psoriasis patient (PS1) were several fold more sensitive to practolol and propranolol than cells derived from normal skin but showed little change in sensitivity towards paracetamol.